The purpose of this project is to determine alterations in bile acid metabolism that occur in patients with diseases of the liver. In this work we have found a defect in the metabolism of the bile acid precursor 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid into cholic acid in two patients with neonatal liver disease. This defect appears to be tansmitted in an autosomal recessive fashion and patients with this problem developed cholestasis and cirrhosis. An asssay system to measure the conversion of this precursor into cholic acid was developed as part of this work and will be used to test the parents of the two children with this disorder. Other studies, carried out in this project, demonstated that cholestyramine plus phenobarbital when given to patients with childhood forms of intrahepatic cholestasis results in the shift of the bile salt pool from the vascular compartment into the enterohepatic circulation. BIBLIOGRAPHIC REFERENCES: Russell F. Hanson, J.N. Isenberg, G.C. Williams, D. Hachey, P. Szczepanik, P.D. Klein and H.L. Sharp. The metabolism of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholestan-26-oic acid in two siblings with cholestasis due to intrahepatic bile duct anomalies: an apparent inborn error of cholic acid synthesis. J. Clin. invest. 56:577-587, 1975. M.D. Levitt, R.F. Hanson, J.H. Bond, and R.R.Engel. Failure to demonstrate degradation of (4-C14) cholesterol to volative hydrocarbon in rats and human fecal homogenates. Lipids 10:662-666, 1975.